Myxoid fibroadenomas differ from conventional fibroadenomas: A hypothesis-generating study Journal Article


Authors: Lozada, J. R.; Burke, K. A.; Maguire, A.; Pareja, F.; Lim, R. S.; Kim, J.; Gularte-Merida, R.; Murray, M. P.; Brogi, E.; Weigelt, B.; Reis-Filho, J. S.; Geyer, F. C.
Article Title: Myxoid fibroadenomas differ from conventional fibroadenomas: A hypothesis-generating study
Abstract: Aims: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs. Methods and results: Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture-microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon histological re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR1A somatic mutation was restricted to the stromal component. Conclusion: MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers. © 2017 John Wiley & Sons Ltd
Keywords: fibroadenoma; med12; msk-impact; breast myxoma; prkar1a
Journal Title: Histopathology
Volume: 71
Issue: 4
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2017-10-01
Start Page: 626
End Page: 634
Language: English
DOI: 10.1111/his.13258
PROVIDER: scopus
PMCID: PMC5597459
PUBMED: 28513873
DOI/URL:
Notes: Article -- Export Date: 4 October 2017 -- Source: Scopus
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MSK Authors
  1. Melissa P Murray
    123 Murray
  2. Edi Brogi
    515 Brogi
  3. Britta Weigelt
    633 Weigelt
  4. Raymond Sear Lim
    57 Lim
  5. Kathleen   Burke
    55 Burke
  6. Jisun Kim
    8 Kim
  7. John Roy Lozada
    20 Lozada